The present application proposes Alcohol, Drug Abuse and Mental Health (ADM) research projects that will enhance the ability of our institution to conduct ADM research. The objectives of this proposal are: 1. To strengthen the institutional infrastructure. 2. To enhance the capability of individual faculty members to perform ADM research. 3. To involve outstanding students in research in order to encourage them to pursue careers in ADM research. The three-dimensional structure and electronic character of (-)-cocaine and (-)-norcocaine will be determined. The effect of commonly prescribed drugs on the hepatotoxicity of cocaine will be investigated in a mouse model. An endogenous ligand of the central benzodiazepine receptor will be identified. The effect of this endogenous ligand on GABA-gated chloride uptake into synaptoneurosomes will be determined. New analogs of anti-AIDS drugs will be synthesized to prevent and treat the mental health effects of AIDS. The bioavailability, metabolic, and blood-brain distribution of these new drugs will be determined. Novel anti-Pneumocystis carinii drugs with less hepatotoxicity will be synthesized to enable improved drug therapy of alcoholic AIDS patients with liver damage. Pharmacokinetic interactions between anti-AIDS and anti-Pneumocystis carinii drugs will be studied. Finally, the effects of chronic alcohol consumption on the appearance of Pneumocystis carinii in a rat model will be determined.